Prevalence of Autoantibodies and HLA DR, DQ in Type 1 Diabetes Mellitus.
Type I diabetes Mellitus (T1DM) is caused by autoimmune destruction of β-cells of pancreas. Two forms of T1DM are known called as 1A (autoimmune) and 1B (idiopathic). Aim was to study the prevalence of Anti-TTG IgA, Anti-TPO, GADA, ZnT8 and IA-2 autoantibodies and HLA DR and DQ genes and its diagnostic value in T1DM. Thirty four T1DM patients, 59 type 2 diabetes mellitus (T2DM) patients and 28 healthy controls were included in study. Antibodies levels were estimated by ELISA and HLA typing was performed by SSP-PCR method. The prevalence of various autoantibodies in T1DM were Anti-TTG 14.7%, Anti-TPO 17.65%, GADA 38.23%, ZnT8 11.76% and IA-2 5.88%. Only GADA and ZnT8 were significantly positive in T1DM. GADA (66.67%) and ZnT8 (33.33%) positivity was more in patients below 15 years age while levels of other antibodies were higher after 15 years age. All autoantibodies were detected in higher frequency in T1DM than in T2DM and controls. HLA DR and DQ typing showed highly significant increase in DRB1*0301 (61.76%, p=0.00) and DQB1*0201 (64.71%, p=0.00) in T1DM. Subjects with HLA DRB1*0301 and DQB1*0201 had 80-100% positive prevalence of GADA, ZnT8, IA-2, Anti-TTG and Anti-TPO autoantibodies. Combination of GADA antibody with DRB1 and DQB1 estimation improved diagnosis of T1A than insulin antigen specific antibodies alone.


Lactation and changes in maternal metabolic risk factors.
To examine the relationship between duration of lactation and changes in maternal metabolic risk factors. This 3-year prospective study examined changes in metabolic risk factors among lactating women from preconception to postweaning and among nonlactating women from preconception to postdelivery, in comparison with nongravid women. Of 1,051 (490 black, 561 white) women who attended two consecutive study visits in years 7 (1992-1993) and 10 (1995-1996), 942 were nongravid and 109 had one interim birth. Of parous women, 48 (45%) did not lactate, and 61 (55%) lactated and weaned before year 10. The lactated and weaned women were subdivided by duration of lactation into less than 3 months and 3 months or more. Multiple linear regression models estimated mean 3-year changes in metabolic risk factors adjusted for age, race, parity, education, and behavioral covariates. Both parous women who did not lactate and parous women who lactated and weaned gained more weight (+5.6, +4.4 kg) and waist girth (+5.3, +4.9 cm) than nongravid women over the 3-year interval; P<.001. Low-density lipoprotein cholesterol (+6.7 mg/dL, P<.05) and fasting insulin (+2.6 microunits, P=.06) increased more for parous women who did not lactate than for nongravid and parous women who lactated and weaned. High-density lipoprotein cholesterol decrements for both parous women who did not lactate and parous women who lactated and weaned were 4.0 mg/dL greater than for nongravid women (P<.001). Among parous, lactated and weaned women, lactation for 3 months or longer was associated with a smaller decrement in high-density lipoprotein cholesterol (-1.3 mg/dL versus -7.3 mg/dL for less than 3 months; P<.01). Lactation may attenuate unfavorable metabolic risk factor changes that occur with pregnancy, with effects apparent after weaning. As a modifiable behavior, lactation may affect women's future risk of cardiovascular and metabolic diseases. II.


An ontology-based tool for the correspondences between specialist and consumer medical lexicons for the geriatrics domain.
New services devoted to improve personalized healthcare are emerging from information technology developments. Personal health record systems allow the patients to participate actively in their healthcare process. However, the dissemination and use of personal health record systems face with some barriers, for example low health literacy that leads to discrepancy in understanding medical concepts. While it is important to present health information using consumer-familiar terms in consumer applications, consistently converting medical terms to consumer-familiar ones is a challenging task. We designed and developed both an ontology-like taxonomic structure devoted to the Geriatrics domain for the outpatient and a software tool, for carrying out the matching between the medical vocabulary of the consumer and that of the doctor from the outpatient's and their family point of view.


beta-Amyloid fibrils activate parallel mitogen-activated protein kinase pathways in microglia and THP1 monocytes.
The senile plaques of Alzheimer's disease are foci of local inflammatory responses, as evidenced by the presence of acute phase proteins and oxidative damage. Fibrillar forms of beta-amyloid (Abeta), which are the primary constituents of senile plaques, have been shown to activate tyrosine kinase-dependent signal transduction cascades, resulting in inflammatory responses in microglia. However, the downstream signaling pathways mediating Abeta-induced inflammatory events are not well characterized. We report that exposure of primary rat microglia and human THP1 monocytes to fibrillar Abeta results in the tyrosine kinase-dependent activation of two parallel signal transduction cascades involving members of the mitogen-activated protein kinase (MAPK) superfamily. Abeta stimulated the rapid, transient activation of extracellular signal-regulated kinase 1 (ERK1) and ERK2 in microglia and ERK2 in THP1 monocytes. A second superfamily member, p38 MAPK, was also activated with similar kinetics. Scavenger receptor and receptor for advanced glycated end products (RAGE) ligands failed to activate ERK and p38 MAPK in the absence of significant increases in protein tyrosine phosphorylation, demonstrating that scavenger receptors and RAGE are not linked to these pathways. Importantly, the stress-activated protein kinases (SAPKs) were not significantly activated in response to Abeta. Downstream effectors of the MAPK signal transduction cascades include MAPKAP kinases, such as RSK1 and RSK2, as well as transcription factors. Exposure of microglia and THP1 monocytes to Abeta resulted in the activation of RSK1 and RSK2 and phosphorylation of cAMP response element-binding protein at Ser133, providing a mechanism for Abeta-induced changes in gene expression.


Stimulation by sparkling water of gastroduodenal HCO3- secretion in rats.
We examined the effect of sparkling water on gastroduodenal HCO3- secretion in rats and investigated the factors involved in these responses. Under urethane anesthesia, a chambered stomach or a proximal duodenal loop was superfused with saline, and HCO3- secretion was measured at pH 7.0 using a pH-stat. The amount of CO2 in sparkling water was about 7.2 g/L. The mucosal exposure with sparkling water increased the secretion of HCO3- in both the stomach and duodenum. The HCO3- response in the duodenum was partially inhibited by indomethacin, acetazolamide or sensory deafferentation and was totally abolished by the co-administration of the former two agents. By contrast, the response in the stomach was almost totally inhibited by acetazolamide and partially mitigated by indomethacin but not sensory deafferentation. DIDS [an inhibitor of the Cl-/HCO3- exchanger (AE) and the Na+-HCO3- cotransporter (NBC)] and DMA [an inhibitor of the Na+/H+ exchanger 1 (NHE1)] partially mitigated the HCO3- response in the duodenum but not the stomach. The mucosal application of sparkling water increased prostaglandin E2 content in these tissues. Sparkling water stimulates HCO3- secretion in both the stomach and the duodenum, but the mechanisms involved differ in these two tissues; the response in the former is mainly due to the intracellular supply of HCO3- with the aid of carbonic anhydrase, while in the latter the response is dependent on the NHE1, AE and NBC, and is mediated by endogenous prostaglandins as well as capsaicin-sensitive afferent neurons, in addition to the intracellular supply of HCO3-.


[Lung cancer in survivors of radiation exposure at the Chernobyl nuclear disaster].
Epidemiology, diagnostics and therapy of lung cancer in the aftermath of Chernobyl nuclear disaster are discussed on the basis of the data released by the Federal Expert Committee. Lung cancer appeared to be the main death-causing factor. The disease was far advanced (stage IIIb and IV) in 85% of cases. The effectiveness of diagnosis can be raised if such compulsory measures as annual bronchoscopic screenings and sputum counts are carried out. Atypical cell counts have to be run in the sputum samples from all the survivors who took part in the salvaging operations of 1986-1987 and are suffering acute and chronic respiratory diseases. Particular attention should be paid to those who were working under severe dust-pollution conditions in summer.


Dental Pulp Stem Cells: Advances to Applications.
Dental pulp stem cells (DPSCs) have a high capacity for differentiation and the ability to regenerate a dentin/pulp-like complex. Numerous studies have provided evidence of DPSCs' differentiation capacity, such as in neurogenesis, adipogenesis, osteogenesis, chondrogenesis, angiogenesis, and dentinogenesis. The molecular mechanisms and functions of DPSCs' differentiation process are affected by growth factors and scaffolds. For example, growth factors such as basic fibroblast growth factor (bFGF), transforming growth factor-β (TGF-β), nerve growth factor (NGF), platelet-derived growth factor (PDGF), and bone morphogenic proteins (BMPs) influence DPSC fate, including in differentiation, cell proliferation, and wound healing. In addition, several types of scaffolds, such as collagen, hydrogel, decellularized bioscaffold, and nanofibrous spongy microspheres, have been used to characterize DPSC cellular attachment, migration, proliferation, differentiation, and functions. An appropriate combination of growth factors and scaffolds can enhance the differentiation capacity of DPSCs, in terms of optimizing not only dental-related expression but also dental pulp morphology. For a cell-based clinical approach, focus has been placed on the tissue engineering triad [cells/bioactive molecules (growth factors)/scaffolds] to characterize DPSCs. It is clear that a deep understanding of the mechanisms of stem cells, including their aging, self-renewal, microenvironmental homeostasis, and differentiation correlated with cell activity, the energy for which is provided from mitochondria, should provide new approaches for DPSC research and therapeutics. Mitochondrial functions and dynamics are related to the direction of stem cell differentiation, including glycolysis, oxidative phosphorylation, mitochondrial metabolism, mitochondrial transcription factor A (TFAM), mitochondrial elongation, and mitochondrial fusion and fission proteins. This review summarizes the effects of major growth factors and scaffolds for regenerating dentin/pulp-like complexes, as well as elucidating mitochondrial properties of DPSCs for the development of advanced applications research.


The Relationship of SUV Value in PET-CT with Tumor Differentiation and Tumor Markers in Gastric Cancer.
We aimed to investigate the relationship between the use of fluoro-2-deoxyglucose (FDG)-positron emission tomography (PET)/computed tomography (CT), maximized standardized uptake value (SUVmax) values of tumors, and tumor differentiation and tumor markers during the initial staging of patients with gastric cancer. The study included 50 patients (14 women and 36 men; mean age: 63±11 years; age range: 31-80 years) who had undergone initial staging with FDG-PET/CT after the diagnosis of gastric cancer with endoscopic biopsy between January and June 2013. Serum alpha fetoprotein (AFP), carcinogenic antigen 19-9 (CA 19.9), carcinoembryonic antigen (CEA), and C-reactive protein (CRP) levels were measured in patients prior to imaging. PET/CT images were evaluated for primary tumors, locoregional spread, and distant organ metastases, and classified by tumor-node-metastasis staging. Semiquantitative data were collected by SUVmax measurements in pathological regions of involvement. Data were analyzed statistically. FDG-PET/CT showed primary gastric cancer with a sensitivity of 87%. Imaging findings were normal in 3 patients (1/3; mucinous adenocarcinoma, 2/3; signet-ring cell adenocarcinoma). With FDG-PET/CT, 3/50 patients were classified into Stage 1B, 3/50 patients into Stage 2, 5/50 patients into Stage 3A, 5/50 patients into Stage 3B, 5/50 patients into 3C and 29/50 patients into Stage 4. The mean SUVmax was calculated as 11.35±4.3 (poorly differentiated adenocarcinoma: 5.4±1.7; moderately differentiated adenocarcinoma: 10.3±4.8) for the primary tumor and 14.9±6.3 for tumor metastasis. A positive correlation was evident between the measured SUVmax and stage and the grade of primary tumor (p<0.05). While the relationship between SUVmax and levels of serum AFP and CRP was statistically significant (p<0.05), the relationship between SUVmax and levels of serum CA 19-9 and CEA was not statistically significant (p>0.05). The SUVmax of primary tumors was associated with the degree of differentiation of primary tumors and the biochemical tumor markers CRP and AFP. The fact that SUVmax of primary tumors is high supplies clues about the presence of the factors affecting prognosis of the disease.


Action Memory and Encoding Time: Evidence for a Strategic View of Action Memory Processing.
The enactment effect is the phenomenon whereby carrying out a simple action phrase results in superior memory compared with listening to the phrase or observing someone else carry out the action. Several early studies suggested that action memory processing is less effortful and strategic compared with traditional verbal processing, a perspective that is still argued today. In the current study, we reexamine a particularly compelling finding in support of this view (Cohen, 1985). Contrary to Cohen's original findings, we demonstrate that additional time to encode an action phrase leads to comparable gains in recall as seen with controls. These data fit well with a different perspective of action memory, namely that the processing of actions is guided by the same strategic, effortful processing as verbal memory.


Nonlinear Analysis of an Unstable Bench Press Bar Path and Muscle Activation.
Lawrence, MA, Leib, DJ, Ostrowski, SJ, and Carlson, LA. Nonlinear analysis of an unstable bench press bar path and muscle activation. J Strength Cond Res 31(5): 1206-1211, 2017-Unstable resistance exercises are typically performed to improve the ability of stabilizing muscles to maintain joint integrity under a load. The purpose of this study was to examine the effects of an unstable load (as provided by a flexible barbell and a load suspended by elastic bands) on the bar path, the primary musculature, and stabilizing musculature while bench pressing using nonlinear analyses. Fifteen resistance-trained men (age 24.2 ± 2.7 years, mass 84.1 ± 12.0 kg, height 1.77 ± 0.05 m, 9.9 ± 3.4 years of lifting experience, and bench press 1 repetition maximum (RM) 107.5 ± 25.9 kg) volunteered for this study. Subjects pressed 2 sets of 5 repetitions in both stable (total load 75% 1RM) and unstable (total load 60% 1RM) conditions using a standard barbell and a flexible Earthquake bar, respectively. Surface electromyography was used to detect muscle activity of primary movers (pectoralis major, anterior deltoid, and triceps) and bar stabilizing musculature (latissimus dorsi, middle and posterior deltoid, biceps brachii, and upper trapezius). During the unstable condition, the bar moved in more ways and was less predictable in the mediolateral and anteroposterior directions. However, the muscle activation patterns of all muscles were more constrained with the unstable barbell. These findings suggest that the unstable condition was more challenging to control, but subjects controlled the instability by contracting their muscles in a more stable pattern or "staying tight" throughout the exercise.


Regulation of NR4A nuclear receptor expression by oncogenic BRAF in melanoma cells.
Activating mutations in the MAPK pathway effectors, NRAS or BRAF, are detected in over 70% of melanomas. Accordingly, the identification of downstream targets of constitutive MAPK signalling in melanoma represents a major goal in understanding the genesis of this disease. We report here the regulation of members of the NR4A family of nuclear receptors by the BRAF-MEK-ERK cascade in melanoma cells. Expression profiling of melanoma cells in which both the NR4A1 and NR4A2 family members have been down-regulated by siRNA revealed alterations in genes associated with proliferation, survival and invasiveness of tumour cells. Notably, the up-regulation of Wnt/β-catenin pathway antagonists, DACT1 and CITED1, following NR4A1/2 ablation suggests a possible link between NR4A and β-catenin activity in melanoma cells. Taken together, these data suggest that dysregulation of NR4A nuclear receptors expression and function by the MAPK pathway may contribute to melanoma tumourigenicity.


The behavioural phenotype of Smith-Magenis syndrome: evidence for a gene-environment interaction.
Behaviour problems and a preference for adult contact are reported to be prominent in the phenotype of Smith-Magenis syndrome. In this study we examined the relationship between social interactions and self-injurious and aggressive/disruptive behaviour in Smith-Magenis syndrome to explore potential operant reinforcement of problem behaviours and thus a gene-environment interaction. Observational data on five children with Smith-Magenis syndrome (age range 3 to 13 years) were collected for between 9 and 12 h. The associations between purported phenotypic behaviours and two environmental events (adult attention and demands) were examined using descriptive analysis. All participants engaged in self-injurious behaviour and aggressive/disruptive outbursts. Sequential analyses of aggressive/disruptive outbursts and self-injury revealed that these behaviours were evoked by low levels of adult attention and led to increased levels of attention following the behaviours in three and two participants respectively out of the four for whom this analysis was possible. Problem behaviour in Smith-Magenis syndrome was evoked by decreased social contact in three out of four children. These data, considered alongside the preference for adult contact and the significantly increased prevalence of these behaviours in Smith-Magenis syndrome, illustrate a potential gene-environment interaction for problem behaviour in this syndrome.


Patient Portals as a Tool for Health Care Engagement: A Mixed-Method Study of Older Adults With Varying Levels of Health Literacy and Prior Patient Portal Use.
Growing evidence that patient engagement improves health outcomes and reduces health care costs has fueled health providers' focus on patient portals as the primary access point for personal health information and patient-provider communication. Whereas much attention has been given to identifying characteristics of older adults who do and do not adopt patient portals and necessary adaptions to portal design, little is known about their attitudes and perceptions regarding patient portal use as a tool for engagement in their health care within the context of health literacy, experience navigating Web-based health information, and previous patient portal use. The specific aims of this study were to explore attitudes toward portal adoption and its perceived usefulness as a tool for health care engagement among adults (65 years and older) who have varying levels of health literacy and degrees of prior patient portal use. A phone survey of 100 community dwelling adults gathered sociodemographic, health, and technology related information. Older adults were purposefully selected for 4 follow-up focus groups based on survey responses to health literacy and previous patient portal use. A mixed-method approach was used to integrate phone survey data with thematic analysis of 4 focus groups. Due to variability in attitudes between focus group participants, an individual case analysis was performed and thematic patterns were used as the basis for subgroup formation. Differences in health literacy, comfort navigating health information on the Web, and previous portal experience explained some but not all differences related to the 7 themes that emerged in the focus groups analysis. Individual cases who shared attitudes were arranged into 5 subgroups from least to most able and willing to engage in health care via a patient portal. The subgroups' overall portal adoption attitudes were: (1) Don't want to feel pushed into anything, (2) Will only adopt if required, (3) Somebody needs to help me, (4) See general convenience of the portal for simple tasks and medical history, but prefer human contact for questions, and (5) Appreciates current features and excited about new possibilities . Most of the older adults are interested in using a patient portal regardless of health literacy level, previous patient portal adoption, or experience navigating health information on the Web. Research targeting informal caregivers of older adults who are unable or unwilling to engage with information technology in health care on their own is warranted. Health care organizations should consider tailored strategies to meet the needs of older adults (and their informal caregivers) and explore alternative workflows that integrate patient portal information into phone conversations and face-to-face contact with health care providers.


Intrafibrillar Mineralization of Self-Assembled Elastin-Like Recombinamer Fibrils.
Biomineralization of bone, a controlled process where hydroxyapatite nanocrystals preferentially deposit in collagen fibrils, is achieved by the interplay of the collagen matrix and noncollagenous proteins. Mimicking intrafibrillar mineralization in synthetic systems is highly attractive for the development of advanced hybrid materials with elaborated morphologies and outstanding mechanical properties, as well as understanding the mechanisms of biomineralization. Inspired by nature, intrafibrillar mineralization of collagen fibrils has been successfully replicated in vitro via biomimetic systems, where acidic polymeric additives are used as analogue of noncollagenous proteins in mediating mineralization. The development of synthetic templates that mimic the structure and functions of collagenous matrix in mineralization has yet to be explored. In this study, we demonstrated that self-assembled fibrils of elastin-like recombinamers (ELRs) can induce intrafibrillar mineralization. The ELRs displayed a disordered structure at low temperature but self-assembled into nanofibrils above its inverse transition temperature. In the presence of the self-assembled ELR fibrils, polyaspartate-stabilized amorphous calcium phosphates preferentially infiltrated into the fibrils and then crystallized into hydroxyapatite nanocrystals with their [001] axes aligned parallel to the long axis of the ELR fibril. As the recombinant technology enables designing and producing well-defined ELRs, their molecular and structural properties can be fine-tuned. By examining the ultrastructure of the self-assembled ELRs fibrils as well as their mineralization, we concluded that the spatial confinement formed by a continuum β-spiral structure in an unperturbed fibrillar structure rather than electrostatic interactions or bioactive sequences in the recombinamer composition played the crucial role in inducing intrafibrillar mineralization.


Folate synthesis in higher-plant mitochondria: coupling between the dihydropterin pyrophosphokinase and the dihydropteroate synthase activities.
The plant enzyme 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase/7,8-dihydropteroate synthase (HPPK/DHPS) is a mitochondrial bifunctional protein involved in tetrahydrofolate synthesis. The first domain (HPPK) catalyses the pyrophosphorylation of 6-hydroxymethyl-7,8-dihydropterin (dihydropterin) by ATP, leading to 6-hydroxymethyl-7,8-dihydropterin pyrophosphate (dihydropterinPP(i)) and AMP. The second domain (DHPS) catalyses the next step, i.e. the condensation of p-aminobenzoic acid (p-ABA) with dihydropterinPP(i) to give 7,8-dihydropteroate (dihydropteroate) and PP(i). In the present article we studied the coupling between these two reactions. Kinetic data obtained for the HPPK domain are consistent with an ordered Bi Bi mechanism where ATP binds first and dihydropterinPP(i) is released last, as proposed previously for the monofunctional Escherichia coli enzyme. In the absence of p-ABA, AMP and dihydropterinPP(i) accumulate and negatively regulate the reaction. In the presence of p-ABA, the rates of AMP and dihydropteroate synthesis are similar, indicating a good coupling between the two reactions. DihydropterinPP(i), an intermediate of the two reactions, never accumulates in this situation. The high specific activity of DHPS relative to HPPK, rather than a preferential channelling of dihydropterinPP(i) between the two catalytic sites, could explain these kinetic data. The maximal velocity of the DHPS domain is limited by the availability of dihydropterinPP(i). It is strongly feedback-inhibited by dihydropteroate and also dihydrofolate and tetrahydrofolate monoglutamate, two intermediates synthesized downstream in the folate biosynthetic pathway. Thus the HPPK domain of this bifunctional protein is the limiting factor of the overall reaction, but the DHPS domain is a potential key regulatory point of the whole folate biosynthetic pathway.


Effect of the acylation of TEAD4 on its interaction with co-activators YAP and TAZ.
The Hippo pathway is deregulated in various cancers, and the discovery of molecules that modulate this pathway may open new therapeutic avenues in oncology. TEA/ATTS domain (TEAD) transcription factors are the most distal elements of the Hippo pathway and their transcriptional activity is regulated by the Yes-associated protein (YAP). Amongst the various possibilities for targeting this pathway, inhibition of the YAP:TEAD interaction is an attractive strategy. It has been shown recently that TEAD proteins are covalently linked via a conserved cysteine to a fatty acid molecule (palmitate) that binds to a deep hydrophobic cavity present in these proteins. This acylation of TEAD seems to be required for efficient binding to YAP, and understanding how it modulates the YAP:TEAD interaction may provide useful information on the regulation of TEAD function. In this report we have studied the effect of TEAD4 acylation on its interaction with YAP and the other co-activator transcriptional co-activator with PDZ-binding motif (TAZ). We show in our biochemical and cellular assays that YAP and TAZ bind in a similar manner to acylated and non-acylated TEAD4. This indicates that TEAD4 acylation is not a prerequisite for its interaction with YAP or TAZ. However, we observed that TEAD4 acylation significantly enhances its stability, suggesting that it may help this transcription factor to acquire and/or maintain its active conformation.


Effect of orlistat on lipid peroxidation, Na+, K+ ATPase, glutathione and serotonin in rat brain.
The aim of this study was to evaluate the effect of orlistat, a drug used in weight loss, on 5-HT and indicators of oxidative stress in rat brain. Orlistat, 12 mg/kg was administered to Wistar rats as single dose or successive doses on 3 consecutive days. Blood glucose and oxidative stress indicators were detected by measurement of lipid peroxidation, Na+, K+ ATPase, glutathione and serotonin levels using previous validated methods. The levels of glucose decreased in rats receiving successive doses. The activity of Na+, K+ ATPase and total ATPase was reduced in rats receiving successive doses, while the level of lipid peroxidation increased slightly in both groups. Glutathione underwent significant reduction in the successive doses group (p < 0.05). 5-HT increased significantly after single dose treatment (p < 0.05). Orlistat can induce pro-oxidant effects in the brain due to alteration of serotonergic metabolism and the reduction of glutathione.


Flavin-enabled reductive and oxidative epoxide ring opening reactions.
Epoxide ring opening reactions are common and important in both biological processes and synthetic applications and can be catalyzed in a non-redox manner by epoxide hydrolases or reductively by oxidoreductases. Here we report that fluostatins (FSTs), a family of atypical angucyclines with a benzofluorene core, can undergo nonenzyme-catalyzed epoxide ring opening reactions in the presence of flavin adenine dinucleotide (FAD) and nicotinamide adenine dinucleotide (NADH). The 2,3-epoxide ring in FST C is shown to open reductively via a putative enol intermediate, or oxidatively via a peroxylated intermediate with molecular oxygen as the oxidant. These reactions lead to multiple products with different redox states that possess a single hydroxyl group at C-2, a 2,3-vicinal diol, a contracted five-membered A-ring, or an expanded seven-membered A-ring. Similar reactions also take place in both natural products and other organic compounds harboring an epoxide adjacent to a carbonyl group that is conjugated to an aromatic moiety. Our findings extend the repertoire of known flavin chemistry that may provide new and useful tools for organic synthesis.


Assessment of the predictive value of clinical and histopathological factors as well as the immunoexpression of p53 and bcl-2 proteins in response to preoperative chemotherapy for esophageal squamous cell carcinoma.
The aim of the study was to determine the predictive value of selected clinical and histopathological factors as well as the immunohistochemical expression of p53 and bcl-2 proteins in the prediction of the pathological response to preoperative chemotherapy in esophageal squamous cell carcinoma. Thirty-four patients with advanced squamous cell carcinoma of the thoracic esophagus (T2-4 N0-1 M0), who underwent one cycle of cisplatin and 5-fluorouracil therapy followed by subtotal esophagectomy, were studied. All clinical factors (tumor longitudinal diameter in a computed tomographic scan, invasion depth, the presence of lymph node metastasis and clinical tumor staging) were evaluated before the onset of the therapy. The histopathological features (grade of differentiation, degree of keratinization, nuclear polymorphism, mitotic index, pattern of cancer invasion and inflammatory response), and the expression of p53 and bcl-2 proteins were also estimated in prechemotherapy endoscopic biopsy specimens. Pathological response to chemotherapy was assessed in surgically resected specimens. Of 34 patients, two (5.9%) showed complete response (CR), six patients (17.6%) exhibited major histological changes (partial response 1; PR1), 24 (70.6%) showed minor histological changes (partial response 2; PR2), and two patients (5.9%) exhibited no response to chemotherapy (stable disease; SD). There were no significant relationships between the response to preoperative chemotherapy (CR + PR1 vs. PR2 + SD) and the majority of the clinical and all the histopathological features. Deeper cancer invasion before chemotherapy was the only factor that tended to worsen the therapy effect (p < 0.01). The pathological response to treatment had no significant associations with the expression of p53 and bcl-2 proteins in esophageal squamous cell carcinoma. It should be noted, however, that both patients in CR were p53 and bcl-2 protein-negative.


Risk factors for traumatic blunt cerebrovascular injury diagnosed by computed tomography angiography in the pediatric population: a retrospective cohort study.
OBJECT Computed tomography angiography (CTA) is frequently used to examine patients for blunt cerebrovascular injury (BCVI) after cranial trauma, but the pediatric population at risk for BCVI is poorly defined. Although CTA is effective for BCVI screening in adults, the increased lifetime risk for malignant tumors associated with this screening modality warrants efforts to reduce its use in children. The authors' objective was to evaluate the incidence of BCVI diagnosed by CTA in a pediatric patient cohort and to create a prediction model to identify children at high risk for BCVI. METHODS Demographic, clinical, and radiographic data were collected retrospectively for pediatric patients who underwent CTA during examination for traumatic cranial injury from 2003 through 2013. The primary outcome was injury to the carotid or vertebral artery diagnosed by CTA. RESULTS The authors identified 234 patients (mean age 8.3 years, range 0.04-17 years, 150 [64%] boys) who underwent CTA screening for BCVI. Of these, 24 (10.3%) had a focal neurological deficit, and 153 (65.4%) had intracranial hemorrhage on a head CTA. Thirty-seven BCVIs were observed in 36 patients (15.4%), and 16 patients (6.8%) died. Multivariate regression analysis identified fracture through the carotid canal, petrous temporal bone fracture, Glasgow Coma Scale (GCS) score of < 8, focal neurological deficit, and stroke on initial CT scan as independent risk factors for BCVI. A prediction model for identifying children at high risk for BCVI was created. A score of ≤ 2 yielded a 7.9% probability of BCVI and a score of ≥ 3 a risk of 39.3% for BCVI. CONCLUSIONS For cranial trauma in children, fracture of the petrous temporal bone or through the carotid canal, focal neurological deficit, stroke, and a GCS score of < 8 are independent risk factors for BCVI.


[Seven-year experience with microsurgery].
From 700 laparoscopies performed, in 600 of them (85.7%) the tuboperitoneal factor was altered. Surgery included: termino-terminal plastia 70 cases (36%), (3 patients had previous plastia); adhensiolysis 62 (31%), salpingostomy 48 (24%), neoimplantation 10 (5%), and mixed surgery 9 (4%). After surgery, desertion was present in 78 patients. Of the 121 remaining, 34 (28.1%) had primary sterility and 87 (71.9%) secondary sterility. 74 patients (61.2%) obtained pregnancy, 62 (83.8%) reached term, seven were abortions of first trimester (9.5%) and were five ectopic pregnancies (6.7%). The interval between surgery and pregnancy achievement was 1 to 48 months, 12.8 months average. We emphasize the 47 patients analysis who didn't has pregnancy, through: remark time after surgery, histerosalpingography, new laparoscopy and reevaluation of sterility factors; the results were: 19 cases (40.5%) have a 5 to 60 months time after surgery, 19.5 months average, 18 (38.3%) had new tubary obstruction, three (6.4%) with endometriosis treatment, three (6.4%) have tuberculosis genital treatment, two (4.2%) with falling again endocrine-ovarian factor, and two (4.2%) with masculine relapse. A decease was present because anesthetic complication. We underline selection surgery criterion and a strictly evaluation, such as an antiadhesion pre, trans and postoperative regime, ligamentopexya of rounds ligaments and a conscious education of the patients in their strictly pursuit.


The tipping point: The critical role of therapeutic apheresis in a case of refractory acquired hemophilia.
Acquired hemophilia A (AHA) is a rare autoimmune disorder that leads to factor VIII (FVIII) deficiency via autoantibody formation. Standard treatment options include FVIII bypassing factors and immunosuppression. However, the role of therapeutic plasma exchange (TPE) is not clear in the treatment of AHA. We present a case of idiopathic AHA in a 66 year old female with severe bleeding and a FVIII inhibitor of 17.6 Bethesda units (BU). She failed to respond to standard treatment including maximum dose of recombinant FVIIa (rFVIIa), rituximab, and other immunosuppressive agents. Her FVIII inhibitor rapidly increased to 140 BU and FVIII was below 5%. TPE was initiated 3 weeks after admission and her bleeding stabilized after the first treatment and completely stopped after three treatments. Repeat testing revealed increased FVIII to 15% and FVIII inhibitor decreased to 2.0 BU. After an additional TPE treatment, her FVIII increased to 27% and FVIII inhibitor decreased to 0.6 BU and she was discharged without bleeding 40 days after admission. In this case, TPE played a critical role in reducing FVIII inhibitor, which resulted in a recovery of FVIII activity and hemostasis. Therefore, TPE should be initiated early in AHA patients with bleeding and high titer of FVIII inhibitor.


Qualitative study of the impact on recovery of peer relationships between female inpatients during treatment for anorexia nervosa in the United Kingdom.
Admissions to hospitals for people with anorexia nervosa (AN) often last over 2 months, during which significant time is often spent with other patients, but there is little qualitative research on the impact on recovery of the inter-patient relationships. Our aim was to conduct qualitative interviews with people with a history of inpatient treatment for AN, focusing on the impact of interactions and relationships between patients during hospital admission on recovery, including short-term and long-term effects. We conducted nine semi-structured, one-to-one interviews, specifically exploring the helpful and unhelpful aspects of inter-patient relationships during inpatient treatment for AN. No type of relationship was either included or excluded. Participants were recruited as volunteers in response to an online advertisement; all who met the eligibility criteria were selected. Interviews were transcribed and analyzed using thematic analysis. Thematic analysis identified five themes: (1) comparison and justification, (2) learnt unhelpful behaviors, (3) dealing with distress, (4) compassion, and (5) role-modeling. All participants expressed conflicting feelings about their relationships with other patients, but generally described developing more resilience to negative effects as they got closer to recovery. Positive effects, such as compassion, appeared to hold significance long term in participants' recovered lives. The detailed exploration of themes in this study provides a deeper understanding of inter-patient relationships during inpatient treatment for AN. This could aid clinical decision-making when choosing appropriate treatment settings for individual patients as well as informing clinical practice in hospital. This study closely examines the effect on recovery of relationships with other patients during hospital treatment for AN, a severe eating disorder. Findings might help hospital staff to understand the feelings of those they look after and develop ways to protect patients from the negative effects of peer relationships and enhance the positive ones, to support recovery in hospital.


AAV-Mediated Expression of Human VEGF, TNF-α, and IL-6 Induces Retinal Pathology in Mice.
Retinopathies display complex pathologies, including vasculopathies, inflammation, and fibrosis, leading ultimately to visual impairment. However, animal models accurately reflecting these pathologies are lacking. In this study, we evaluate the suitability of using Adeno-associated virus (AAV)-mediated long-term expression of cytokines to establish retinal pathology in the murine retina. We administered recombinant, Müller-glia targeted AAV-ShH10 into the mouse vitreous to induce retinal expression of either human vascular endothelial growth factor (VEGF)-A165, tumor necrosis factor alpha (TNF-α), or interleukin-6 (IL-6) and evaluated consequent effects by optical coherence tomography, fluorescein angiography, and histology. Intravitreal injection of AAVs resulted in rapid and stable expression of the transgenes within 1 to 6 weeks. Akin to the role of VEGF-A in wet age-related macular degeneration, expression of VEGF-A led to several vasculopathies in mice, including neovascularization and vascular leakage. In contrast, the expression of the proinflammatory cytokines TNF-α or IL-6 induced retinal inflammation, as indicated by microglial activation. Furthermore, the expression of TNF-α, but not of IL-6, induced immune cell infiltration into the vitreous as well as vasculitis, and subsequently induced the development of fibrosis and epiretinal membranes. In summary, the long-term expression of human VEGF-A165, TNF-α, or IL-6 in the mouse eye induced specific pathologies within 6 weeks that mimic different aspects of human retinopathies. AAV-mediated expression of human genes in mice is an attractive approach to provide valuable insights into the underlying molecular mechanisms causing retinopathies and is easily adaptable to other genes and preclinical species supporting drug discovery for retinal diseases.


Specific detection of unamplified mycobacterial DNA by use of fluorescent semiconductor quantum dots and magnetic beads.
Here we present the development of a specific DNA detection method using fluorescent semiconductor quantum dots (QDs) and magnetic beads (MBs) for fast detection of Mycobacterium spp., dispensing with the need for DNA amplification. Two biotinylated oligonucleotide probes were used to recognize and detect specific complementary mycobacterial target DNA through a sandwich hybridization reaction. Cadmium selenite QDs conjugated with streptavidin and species-specific probes were used to produce a fluorescent signal. MBs conjugated with streptavidin and a genus-specific probe were used to isolate and concentrate the DNA targets. The application of the proposed method to isolated bacteria produced the expected result in all cases. The minimum detection limit of the assay was defined as 12.5 ng of DNA diluted in a sample volume of 20 microl. In order to obtain an indication of the method's performance with clinical samples, we applied the optimized assay to the detection of Mycobacterium tuberculosis in DNA isolated from bronchoalveolar lavage specimens from patients with tuberculosis and Mycobacterium avium subsp. paratuberculosis in DNA isolated from feces and paraffin-embedded tissues in comparison with culture, Ziehl-Neelsen staining, and real-time PCR. The concordance of these methods compared to the proposed method with regard to positive and negative samples varied between 53.84% and 87.23% and between 84.61% and 100%, respectively. The overall accuracy of the QD assay compared to real-time PCR was 70 to 90% depending on the type of clinical material. The proposed diagnostic assay offers a simple, rapid, specific, and cost-effective method for direct detection and identification of mycobacterial DNA in clinical samples.


Topical administration of cyclosporine for treatment of keratoconjunctivitis sicca in dogs.
Sixty dogs with chronic keratoconjunctivitis sicca were treated by topical administration of 2% cyclosporine twice daily. Causes and duration of keratoconjunctivitis varied. Tear production improved in 75 of 100 eyes, and corneal pigmentation decreased in 45 of 67 eyes. Six factors were evaluated to determine their influence on treatment outcome. The only significant variable was the initial Schirmer tear test value. Side effects were few. Evidence of burning in response to application of cyclosporine resolved with change in the formulation of the topical solution.


Systematic Administration of B Vitamins Alleviates Diabetic Pain and Inhibits Associated Expression of P2X3 and TRPV1 in Dorsal Root Ganglion Neurons and Proinflammatory Cytokines in Spinal Cord in Rats.
Treatment of diabetic neuropathic pain (DNP) continues to be a major challenge, and underlying mechanisms of DNP remain elusive. We investigated treatment effects of B vitamins on DPN- and DNP-associated alterations of neurochemical signaling in the nociceptive dorsal root ganglion (DRG) neurons and the spinal cord in rats. DNP was produced in male, adult, Sprague Dawley rats by single i.p. streptozotocin (STZ). Western blot analysis and immunohistochemistry were used to analyze protein expressions in DRG and ELISA to measure the proinflammatory cytokines in the spinal cord. Behaviorally expressed DNP was determined by measuring the sensitivity of hindpaw skin to mechanical and thermal stimulation. There were 87.5% (77/88) rats which developed high blood glucose within 1-2 weeks following STZ injection. Of which, 70.13% (n = 54/77) animals exhibited DNP manifested as mechanical allodynia and/or thermal hyperalgesia. Intraperitoneal administration of vitamins B1/B6/B12 (100/100/2 mg/kg, one or multiple doses) significantly attenuated DNP without affecting the blood glucose. Expressions of P2X3 and TRPV1 in CGRP-positive and IB4-positive DRG neurons as well as the interleukin-1β, tumor necrosis factor-α, and nerve growth factor in the lumbar spinal cord were greatly increased in DNP rats. Such DNP-associated neurochemical alterations were also greatly suppressed by the B-vitamin treatment. B-vitamin treatment can greatly suppress chronic DNP and DNP-associated increased activities of P2X3 and TRPV1 in DRG and the spinal proinflammatory cytokines, which may contribute to the pathogenesis of DNP. Systematic administration of B vitamins can be a strategy for DNP management in clinic.


[The expression of arrhythmic related genes on Xenopus oocytes for evaluation of class III antiarrhythmic drugs from ocean active material].
By techniques of gene clone, microinjection and patch-clamp, human arrhythmic related gene Kv1.5 and Kv4.2 are translated mRNA, and injected into Xenopus Oocytes, respectively. A pure and single K+ current of ultrarapid delayed rectifier K+ current (Ikur) or transient outward K+ current (Ito) is respectively expressed on Xenopus Oocytes. This is a modern pharmacological model for evaluation class III antiarrhythmic drugs, overcomes many defects such as lacking human fresh cardiac muscle cells as material and co-expression of many currents on cell membrane. A new compound A1998 from Ocean material is evaluated in this model for class III antiarrhythmic functions.


Brain iron concentrations in the pathophysiology of children with attention deficit/hyperactivity disorder: a systematic review.
Attention deficit/hyperactivity disorder (ADHD) is a neurological disorder associated with iron dysregulation in children. Although previous focus was on examining systemic iron status, brain iron content may be a more reliable biomarker of the disorder. This systematic review examines whether children with ADHD have lower serum as well as brain iron concentrations, compared with healthy control subjects (HCS). A systematic literature search was conducted in Medline via PubMed, the Cochrane Library, Web of Science, Embase. and Ovid for papers published between 2000 and June 7, 2019. Studies were included if the mean difference of iron concentration, measured as serum iron, serum ferritin, or brain iron, between children with ADHD and HCS was an outcome measure. Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed. Risks of bias within and between studies were assessed using the quality assessment tools of the National Institutes of Health. Of 599 records screened, 20 case-control studies met the inclusion criteria. In 10 of 18 studies in which serum ferritin concentration was assessed, and 2 of 10 studies that assessed serum iron, a significant difference between children with ADHD and HCS was observed. Results of systemic iron levels were inconsistent. In 3 studies in which brain iron concentration was assessed, a statistically significant, lower thalamic iron concentration was found in children with ADHD than in HCS. The evidence, though limited, reveals that brain iron rather than systemic iron levels may be more associated with the pathophysiology of ADHD in children. Larger, longitudinal, magnetic resonance imaging studies are needed to examine any correlations of iron deficiency in specific brain regions and symptoms of ADHD.


Rivaroxaban for stroke prevention in East Asian patients from the ROCKET AF trial.
In Rivaroxaban Once Daily Oral Direct Factor Xa Inhibitor Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF) trial, rivaroxaban was noninferior to dose-adjusted warfarin in preventing stroke or systemic embolism among patients with nonvalvular atrial fibrillation at moderate to high stroke risk. Because of differences in patient demographics, epidemiology, and stroke risk management in East Asia, outcomes and relative effects of rivaroxaban versus warfarin were assessed to determine consistency among East Asians versus other ROCKET AF participants. Baseline demographics and interaction of treatment effects of rivaroxaban and warfarin among patients within East Asia and outside were assessed. A total of 932 (6.5%) ROCKET AF participants resided in East Asia. At baseline, East Asians had lower weight, creatinine clearance, and prior vitamin K antagonist use; higher prevalence of prior stroke; and less congestive heart failure and prior myocardial infarction than other participants. Despite higher absolute event rates for efficacy and safety outcomes in East Asians, the relative efficacy of rivaroxaban (20 mg once daily; 15 mg once daily for creatinine clearance of 30-49 mL/min) versus warfarin with respect to the primary efficacy end point (stroke/systemic embolism) was consistent among East Asians and non-East Asians (interaction P=0.666). Relative event rates for the major or nonmajor clinically relevant bleeding in patients treated with rivaroxaban and warfarin were consistent among East Asians and non-East Asians (interaction P=0.867). Observed relative efficacy and safety of rivaroxaban versus warfarin were similar among patients within and outside East Asia. Rivaroxaban, 20 mg once daily, is an alternative to warfarin for stroke prevention in East Asians with nonvalvular atrial fibrillation.


Racial, Ethnic, Nativity, and Educational Disparities in Cognitive Impairment and Activity Limitations in the United States, 1998-2016.
Despite extensive research on cognitive impairment and limitations in basic activities of daily living, no study has investigated the burden of their co-occurrence (co-impairment). Using the Health and Retirement Study data and incidence-based multistate models, we study the population burden of co-impairment using three key indicators: mean age at onset, lifetime risk, and health expectancy. We examine patterns by gender, race, ethnicity, nativity, education, and their interactions for U.S. residents aged 50-100. Furthermore, we analyze what fractions of racial, ethnic, and nativity disparities in co-impairment are attributable to inequalities in educational attainment. Results reveal that an estimated 56% of women and 41% of men aged 50 will experience co-impairment in their remaining life expectancy. Men experience an earlier onset of co-impairment than women (74 vs. 77 years), and women live longer in co-impairment than men (3.4 vs. 1.9 years). Individuals who are Black, Latinx, and lower educated, especially those experiencing intersecting disadvantages, have substantially higher lifetime risk of co-impairment, earlier co-impairment onset, and longer life in co-impairment than their counterparts. Up to 75% of racial, ethnic, and nativity disparity is attributable to inequality in educational attainment. This study provides novel insights into the burden of co-impairment and offers evidence of dramatic disparities in the older U.S. population.


Clostridium difficile: an emerging epidemic in nursing homes.
Clostridium difficile is currently recognized as the most common cause of nosocomial infectious diarrhea in the nursing home setting. Data from the Centers for Disease Control and Prevention confirm that the incidence of C. difficile has doubled in recent years and accounts for approximately 3 million cases of diarrhea and colitis each year. Overall mortality associated with C. difficile infectious diarrhea is estimated to be 17% but is even higher in the older adult population. Older adults are at higher risk for this infection because of age-related changes in fecal flora and host defenses, as well as the presence of multiple comorbidities. Nursing staff, nurse practitioners, and physicians must become knowledgeable in the treatment and management of C. difficile before it reaches epidemic proportions. Diligent infection control practices, health care worker education, family education, and identification of new prevention and control strategies are vital to limiting its spread.


Utilization of telehealth to manage the Covid-19 pandemic in low- and middle-income countries: a scoping review.
Recently, the coronavirus disease 2019 (Covid-19) pandemic has led to an increase in the use of telehealth technology. It seems that the application of this technology in low- and middle-income countries (LMICs) has been limited, and few studies have been undertaken to review the current state of knowledge in this area. The aim of the present study was to explore the utilization of telehealth to manage the Covid-19 pandemic in LMICs. This scoping review was conducted in 2022. PubMed, Web of Science, Scopus, the Cochrane Library, IEEE Xplore, and ProQuest were searched, and all quantitative research, qualitative studies, case reports, and case studies related to the use of telehealth to manage Covid-19 in LMICs and published since 2020 were included in the study. The findings were analyzed and reported narratively. In total, 18 articles were included in the research. These studies were conducted in South Asia, sub-Saharan Africa, the Middle East and North Africa, and East Asia and Oceania. Telehealth interventions included teleconsultation, telecoaching, teledermatology, televisit, mhealth applications, telerehabilitation, telepharmacy, and telepsychiatry. WhatsApp was the most common way for service delivery and in most studies, patients and health care providers were satisfied with services. Although the use of telehealth interventions was limited in LMICs during the Covid-19 pandemic, in most cases, it was an effective solution to combat the outbreak of Covid-19 and had positive outcomes. A comparison between the characteristics and clinical effectiveness of similar interventions in different countries including LMICs are worth investigation in the future studies.


Predictors of mortality in patients with an implantable cardiac defibrillator: a systematic review and meta-analysis.
Many current predictors of mortality in heart failure (HF) were evaluated before the use of implantable cardioverter defibrillators (ICDs). We conducted a meta-analysis to identify factors associated with mortality in ICD-HF patients. We searched in MedLine, EMBASE, and CINAHL in May 2012. Two reviewers selected citations that included ambulatory ICD patients and addressed the association between any predictor and mortality using multivariable regression. We meta-analyzed mortality using random-effects models. Of 10,420 studies reviewed, 72 studies evaluating 63 predictors on 257,692 ICD patients proved eligible. High confidence in estimates was found for age (hazard ratio [HR], 1.45 for 10-year increase; 95% confidence interval [CI], 1.35-1.56), baseline glomerular filtration rate (HR, 1.25 for 15-mL/min decrease; 95% CI, 1.15-1.35), chronic obstructive pulmonary disease (HR, 1.54; 95% CI, 1.38-1.71), diabetes (HR, 1.56; 95% CI, 1.37-1.79), peripheral vascular disease (HR, 1.43; 95% CI, 1.2-1.72), left ventricular ejection fraction (HR, 0.77 for 10% increase; 95% CI, 0.73-0.83), and appropriate or inappropriate ICD shocks (HR, 2.34; 95% CI 1.59-3.44) New York Heart Association class, atrial fibrillation, and congestive HF were strongly associated with mortality but the confidence in estimates was low. Ischemic cardiomyopathy and male sex were not independent predictors of mortality. This meta-analysis identified strong reliable mortality predictors in ICD-HF patients. Age, renal dysfunction, chronic obstructive pulmonary disease, diabetes, peripheral vascular disease, decreased left ventricular ejection fraction, and ICD shocks during follow-up were strong predictors of mortality; ischemic cardiomyopathy and male sex were not. Further research is needed to study other potential predictors, particularly biomarkers.


Effect of crystalloid cardioplegic solution at different calcium concentration on immature myocardium.
To determine the myocardial protective effect of crystalloid cardioplegic solution at different calcium concentration on immature myocardium. Isolated perfused neonatal rabbit hearts from three groups, arrested by intermittent infusion of St. Thomas II cardioplegic solution with different concentration of calcium (in each group, only calcium concentration of cardioplegic solution was modified, I. [Ca2+] 0.6 mmol/L; II. [Ca2+] 1.2 mmol/L; III. [Ca2+] 2.4 mmol/L), were kept ischemic globally at 20 degrees C for 90 minutes and then followed by 30 minutes of reperfusion in Langendorff mode. Although the recovery of LVDP, +dp/dtmax at calcium content of 2.4 mmol/L after 10 minutes of reperfusion was significantly higher than those at 0.6 and 1.2 mmol/L calcium (P < 0.05, P < 0.01, respectively). The declined tendency of left ventricular hemodynamics after 20 minutes of reperfusion in this group was detected. By the end of reperfusion, the left ventricular functional recovery at 2.4 mmol/L calcium did not differ from those at 1.2 and 0.6 mmol/L calcium. Conversely, postischemic left ventricular functions at 0.6 and 1.2 mmol/L calcium were gradually improved during 30 minutes of reperfusion. In 2.4 mmol/L calcium group, the Ca(2+)-ATPase activity significantly increased (P < 0.01, P < 0.001) whereas myocardial ATP content was lower when compared with 1.2 mmol/L (P < 0.001) and 0.6 mmol/L calcium groups. Our research demonstrated that there were no statistical differences with respect to hemodynamic recovery in three groups after 30 minutes of reperfusion although left ventricular functional recovery at 2.4 mmol/L calcium accelerated early after reperfusion. In addition, with 2.4 mmol/L calcium, myocardial ATP content was decreased significantly. We conclude that, from the point of view of myocardial energy metabolism, St. Thomas II cardioplegic solution at high concentration of calcium can not provide immature myocardium with optimal myocardial protection while with 1.2 mmol/L calcium, however, better high-energy store can be preserved.


Music therapy increases serum melatonin levels in patients with Alzheimer's disease.
Music therapy is known to have healing and relaxing effects. Although these effects appear to be mediated by release of neurotransmitters and neurohormones, the specific neurohormonal systems involved have not been fully investigated. To assess the effects of a music therapy intervention on concentrations of melatonin, norepinephrine, epinephrine, serotonin, and prolactin in the blood of a group of patients with Alzheimer's disease. Blood samples were obtained before initiating the therapy, immediately at the end of 4 weeks of music therapy sessions, and at 6 weeks follow-up after cessation of the sessions. Miami Veterans Administration Medical Center, Miami, Fla. 20 male inpatients with Alzheimer's disease. 30- to 40-minute morning sessions of music therapy 5 times per week for 4 weeks. Changes in melatonin, norepinephrine, epinephrine, serotonin, and prolactin following music therapy. Melatonin concentration in serum increased significantly after music therapy and was found to increase further at 6 weeks follow-up. A significant increase was found between baseline values and data recorded after the music therapy sessions as well as at 6 weeks follow-up. Norepinephrine and epinephrine levels increased significantly after 4 weeks of music therapy, but returned to pretherapy levels at 6 weeks follow-up. Serum concentration of prolactin and platelet serotonin levels remained unchanged after 4 weeks of music therapy and at 6 weeks follow-up. Increased levels of melatonin following music therapy may have contributed to patients' relaxed and calm mood.


Mapping of two novel transcripts of bovine papillomavirus type 4.
A cDNA library was synthesized using RNA from bovine papillomavirus type 4 (BPV-4)-induced papillomas. The major viral transcript was characterized by sequencing of its cDNA, primer extension mapping and S1 nuclease protection studies. The transcript initiates at multiple sites between nucleotide (nt) 777 and nt 902, contains a splice junction between nt 1016 and nt 3376 and terminates at nt 4034, using the early polyadenylation signal at nt 4009. Sequencing of viral cDNAs and mRNA revealed deviations from the reported genomic sequence between nt 3412 and nt 3460. These resulted in a temporary frameshift, abolished the translation termination codon of the E5a open reading frame (ORF), and introduced a new termination codon in the E4 ORF. The new uninterrupted E5 ORF was found to have greater homology to the E4 ORFs of other papillomaviruses than to their E5 ORFs. The E5 ORF of BPV-4 is joined to a five codon ORF in the leader exon of the major transcript, in the same way as the E4 ORF in the major transcripts of BPV-1 and human papillomavirus type 11. On this basis, it has been redesignated E4, and the viral genomic sequence revised. Two novel transcriptional promoters of BPV-4 were defined: a putative controller of the multiple major RNA start sites around nt 870 and a minor TATA box at nt 691. In addition, minor early region transcripts were mapped which initiate between nt 3071 and nt 3152. None of these transcripts utilizes the splice site at nt 3376. These messages may express E2-encoded functions.


[The effect of polymorphisms of the angiotensin-converting enzyme and angiotensinogen genes on the phenotypic expression of Spanish patients with hypertrophic cardiomyopathy].
Hypertrophic cardiomyopathy (HCM) has a great variability in its morphofunctional expression. This study analyzes whether angiotensin-converting enzyme (ACE) and angiotensinogen (AGT) gene polymorphisms modulate the phenotypic expression in Spanish patients with HCM. Forty Spanish HCM patients were studied. Twenty-six out of these 40 patients belonged to 7 families with familial HCM, and the remaining 14 patients had either a sporadic HCM or a HCM with unknown family incidence. A group of 269 healthy subjects was included as control for the genotype study. Maximal wall thickness, ventricular mass and several diastolic function indexes were measured in each patient by Doppler-echocardiography. The insertion/deletion (I/D) polymorphism of ACE gene and the M235T polymorphism of AGT gene were studied in both patients and healthy subjects. A higher frequency in patients than in controls was found for D allele (0.79 vs 0.64; p = 0.02) and for DD genotype (62.5 vs 41.2%; p = 0.02). Conversely, no difference was observed in M235T polymorphism between both groups. Neither DD genotype of ACE, nor TT genotype of AGT determined a greater degree of ventricular hypertrophy or a worse diastolic function in patients with HCM. D allele and DD genotype are predisposing factors to express HCM. In this series of Spanish patients, I/D polymorphism of ACE and M235T polymorphism of AGT do not modify phenotypic expression of HCM.


Dietary Inflammatory Index and Colorectal Cancer Risk-A Meta-Analysis.
Diet and chronic inflammation of the colon have been suggested to be risk factors in the development of colorectal cancer (CRC). The possible link between inflammatory potential of diet, measured through the Dietary Inflammatory Index (DII®), and CRC has been investigated in several populations across the world. The aim of this study was to conduct a meta-analysis on studies exploring this association. Data from nine studies were eligible, of which five were case-control and four were cohort studies. Results from meta-analysis showed a positive association between increasing DII scores, indicating a pro-inflammatory diet, and CRC. Individuals in the highest versus the lowest (reference) DII category showed an overall 40% increased risk of CRC with moderate evidence of heterogeneity [relative risk (RR) = 1.40, 95% confidence interval (CI): 1.26, 1.55; I² = 69%, p < 0.001]. When analyzed as a continuous variable, results showed an increased risk of CRC of 7% for a 1-point increase in the DII score. Results remained unchanged when analyses were restricted to the four prospective studies. Results of our meta-analysis support the importance of adopting a healthier anti-inflammatory diet in preventing CRC. These results further substantiate the utility of DII as tool to characterize the inflammatory potential of diet and to predict CRC.


Bonding Motifs in Metal-Organic Compounds on Surfaces.
The bonds in metal organic networks on surfaces govern the resulting geometry as well as the electronic properties. Here, we study the nature of these bonds by forming phenazine-copper complexes on a copper surface by means of atomic manipulation. The structures are characterized by a combination of scanning probe microscopy and density functional theory calculations. We observed an increase of the molecule-substrate distance upon covalent bond formation and an out-of-plane geometry that is in direct contradiction with the common expectation that these networks are steered by coordination bonds. Instead, we find that a complex energy balance of hybridization with the substrate, inhomogeneous Pauli repulsion, and elastic deformation drives the phenazine-copper interaction. Most remarkably, this attractive interaction is not driven by electron acceptor properties of copper but is of completely different donation/back-donation mechanism between molecular π-like orbitals and sp-like metal states. Our findings show that the nature of bonds between constituents adsorbed on surfaces does not have to follow the common categories.


Prevalence of Plasmid-Mediated Fosfomycin Resistance Gene fosA3 Among CTX-M-Producing Escherichia coli Isolates from Chickens in China.
The aim of this study was to investigate the prevalence of fosfomycin resistance gene fosA3 and characterize plasmids harboring fosA3 among CTX-M-producing Escherichia coli from chickens in China. A total of 234 CTX-M-producing E. coli isolates collected from chickens from 2014 to 2016 were screened for the presence of plasmid-mediated fosfomycin resistance genes (fosA, fosA3, and fosC2). Clonal relatedness of fosA3-positive isolates was determined by pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST). The genetic environment of fosA3 was analyzed by polymerase chain reaction (PCR) mapping. Plasmids were studied by using conjugation experiments, PCR-based replicon typing and plasmid MLST. Sixty-four (27.4%) fosA3-positive E. coli isolates were identified in this study. The gene blaCTX-M-55 (31/64) was predominant among these strains, followed by blaCTX-M-14 (18/64) and blaCTX-M-65 (14/64). Various PFGE patterns and sequence types (STs) indicated that these isolates were clonally unrelated. Seven different genetic environments of fosA3 were identified and two new combinations (ISEcp1-blaCTX-M-65-ΔIS903D-IS26-fosA3-orf1-orf2-Δorf3-IS26 and IS26-ISEcp1-blaCTX-M-3-orf477-blaTEM-1-IS26-fosA3-orf1-orf2-Δorf3-IS26) were discovered for the first time. Conjugation experiments were successful for 47 isolates and 33 transconjugants harbored a single plasmid. Plasmids carrying fosA3 belonged to incompatibility group IncFII (17/33), IncI1 (2/33), IncHI2 (3/33), and IncB/O (1/33). F33:A-:B- plasmids carrying blaCTX-M-55, IncHI2/ST3 plasmids carrying blaCTX-M-65, and F2:A-:B-plasmids carrying blaCTX-M-55 were found in E. coli isolates from different provinces. Our results revealed a considerable prevalence of fosA3 gene among CTX-M-producing E. coli with clonal diversity from chickens in China. The transmission of different kinds of plasmids is responsible for the dissemination of fosA3 in chicken farms in China.


Selective treatment of nonsevere clinical mastitis does not adversely affect cure, somatic cell count, milk yield, recurrence, or culling: A systematic review and meta-analysis.
Treatment of clinical mastitis (CM) contributes to antimicrobial use on dairy farms. Selective treatment of CM based on bacterial diagnosis can reduce antimicrobial use, as not all cases of CM will benefit from antimicrobial treatment, e.g., mild and moderate gram-negative infections. However, impacts of selective CM treatment on udder health and culling are not fully understood. A systematic search identified 13 studies that compared selective versus blanket CM treatment protocols. Reported outcomes were synthesized with random-effects models and presented as risk ratios or mean differences. Selective CM treatment protocol was not inferior to blanket CM treatment protocol for the outcome bacteriological cure. Noninferiority margins could not be established for the outcomes clinical cure, new intramammary infection, somatic cell count, milk yield, recurrence, or culling. However, no differences were detected between selective and blanket CM treatment protocols using traditional analyses, apart from a not clinically relevant increase in interval from treatment to clinical cure (0.4 d) in the selective group and higher proportion of clinical cure at 14 d in the selective group. The latter occurred in studies co-administering nonsteroidal anti-inflammatories only in the selective group. Bias could not be ruled out in most studies due to suboptimal randomization, although this would likely only affect subjective outcomes such as clinical cure. Hence, findings were supported by a high or moderate certainty of evidence for all outcome measures except clinical cure. In conclusion, this review supported the assertion that a selective CM treatment protocol can be adopted without adversely influencing bacteriological and clinical cure, somatic cell count, milk yield, and incidence of recurrence or culling.


Opening up: psychiatric nurses' experiences of participating in reflection groups focusing on the use of coercion.
Psychiatric staff report that the use of coercion towards patients in psychiatric care engenders feelings of discomfort and conflicts. The aim of this study was to describe psychiatric nurses' experiences of participating in reflection groups focused on the use of coercion, in relation to their views regarding systematic clinical supervision and staff support. Twenty-one nurses who had participated in reflection groups were interviewed retrospectively. The structured interview focused on: (i) their views of clinical supervision and support in general; (ii) their views of clinical supervision and support specifically concerning the use of coercion; and (iii) their experiences of participating in groups reflecting the use of coercion. Nurses were largely positive about participating in reflection groups, as expressed in the subthemes: having time for reflection; being confirmed; gaining new perspectives; sharing fellowship with colleagues; and relating more effectively to patients. Complications concerning participation in the reflection groups and other forms of clinical supervision as reported by nurses were: providing time for participation; having a common aim; being vulnerable in difficult situations; and assuming that the need for supervision and support could indicate that they were not coping with their job.


Concentration of Micro- and Macro-Elements in Green and Roasted Coffee: Influence of Roasting Degree and Risk Assessment for the Consumers.
The aim of the present study was to determine concentrations of 15 macro- and micro-elements in 10 commercially available plantation Arabica coffee brands. The elemental concentration was studied in 50 samples of green and roasted coffee beans of various roasting degrees and their infusions. There were four different roasting degrees: City + (C+), Full city (FC), Full city ++ (FC++), and Dark (D). The attention was given to the impact of the roasting process on the elemental composition. Statistically significant differences were found between the green coffee beans and the different roasting degrees in both macro- and micro-elements. The results showed that roasting degrees affected the concentration of elements in resulting infusions. Dietary intakes for macro- and micro-elements based on RDA and PTWI (in the case of Al) were calculated. Based on the RDA values for macro- and micro-elements, it can be concluded that coffee infusions are not an important source of elements in nutrition. In the case of Al, consumption of coffee was considered non-hazardous based on the PTWI value.


Wide-ranging and unexpected consequences of altered Pol II catalytic activity in vivo.
Here we employ a set of RNA Polymerase II (Pol II) activity mutants to determine the consequences of increased or decreased Pol II catalysis on gene expression in Saccharomyces cerevisiae. We find that alteration of Pol II catalytic rate, either fast or slow, leads to decreased Pol II occupancy and apparent reduction in elongation rate in vivo. However, we also find that determination of elongation rate in vivo by chromatin immunoprecipitation can be confounded by the kinetics and conditions of transcriptional shutoff in the assay. We identify promoter and template-specific effects on severity of gene expression defects for both fast and slow Pol II mutants. We show that mRNA half-lives for a reporter gene are increased in both fast and slow Pol II mutant strains and the magnitude of half-life changes correlate both with mutants' growth and reporter expression defects. Finally, we tested a model that altered Pol II activity sensitizes cells to nucleotide depletion. In contrast to model predictions, mutated Pol II retains normal sensitivity to altered nucleotide levels. Our experiments establish a framework for understanding the diversity of transcription defects derived from altered Pol II activity mutants, essential for their use as probes of transcription mechanisms.


From analytic to synthetic-organizational pluralisms: A pluralistic enactive psychiatry.
Reliance on sole reductionism, whether explanatory, methodological or ontological, is difficult to support in clinical psychiatry. Rather, psychiatry is challenged by a plurality of approaches. There exist multiple legitimate ways of understanding human functionality and disorder, i.e., different systems of representation, different tools, different methodologies and objectives. Pluralistic frameworks have been presented through which the multiplicity of approaches in psychiatry can be understood. In parallel of these frameworks, an enactive approach for psychiatry has been proposed. In this paper, we consider the relationships between the different kinds of pluralistic frameworks and this enactive approach for psychiatry. We compare the enactive approach in psychiatry with wider analytical forms of pluralism. On one side, the enactive framework anchored both in cognitive sciences, theory of dynamic systems, systems biology, and phenomenology, has recently been proposed as an answer to the challenge of an integrative psychiatry. On the other side, two forms of explanatory pluralisms can be described: a non-integrative pluralism and an integrative pluralism. The first is tolerant, it examines the coexistence of different potentially incompatible or untranslatable systems in the scientific or clinical landscape. The second is integrative and proposes to bring together the different levels of understanding and systems of representations. We propose that enactivism is inherently a form of integrative pluralism, but it is at the same time a component of the general framework of explanatory pluralism, composed of a set of so-called analytical approaches. A significant number of mental health professionals are already accepting the variety of clinical and scientific approaches. In this way, a rigorous understanding of the theoretical positioning of psychiatric actors seems necessary to promote quality clinical practice. The study of entanglements between an analytical pluralism and a synthetic-organizational enactivist pluralism could prove fruitful.


Synthetic aperture inversion for arbitrary flight paths and nonflat topography.
This paper considers synthetic aperture radar (SAR) and other synthetic aperture imaging systems in which a backscattered wave is measured from positions along an arbitrary (known) flight path. The received backscattered signals are used to produce an image of the terrain. We assume a single-scattering model for the radar data, and we assume that the ground topography is known but not necessarily flat. We focus on cases in which the antenna footprint is so large that the standard narrow-beam algorithms are not useful. We show that certain artifacts can be avoided if the antenna and antenna footprint avoid particular relationships with the ground topography. We give an explicit backprojection imaging algorithm that corrects for the ground topography, flight path, antenna beam pattern, source waveform, and other geometrical factors. For the case of a non-directional antenna, the image produced by the above algorithm contains artifacts. For this case, we analyze the strength of the artifacts relative to the strength of the true image. The analysis shows that the artifacts can be somewhat suppressed by increasing the frequency, integration time, and the curvature of the flight path.


Test-charge theory for the electric double layer.
We present a model for the ion distribution near a charged surface, based on the response of the ions to the presence of a single test particle. Near an infinite planar surface this model produces the exact density profile in the limits of weak and strong coupling, which correspond to zero and infinite values of the dimensionless coupling parameter. At intermediate values of the coupling parameter our approach leads to approximate density profiles that agree qualitatively with Monte Carlo simulation. For large values of the coupling parameter our model predicts a crossover from exponential to algebraic decay at large distance from the charged plate. Based on the test-charge approach we argue that the exact density profile is described, in this regime, by a modified mean-field equation, which takes into account the interaction of an ion with the ions close to the charged plate.


Use of secondary prophylaxis against myocardial infarction in the north of England.
To record the use of secondary prophylactic drugs in patients discharged from hospital having had a myocardial infarction. Prospective postal questionnaire survey of a random one in two sample of general practitioners in the region. The nine family practitioner committee areas within the Northern Regional Health Authority. Patients who had had a myocardial infarction and were discharged to their general practitioner. Whether beta blockers or aspirin, or both, were given on discharge. Of 267 patients, 158 (59%) were treated suboptimally in that they did not receive a secondary prophylactic drug to which they had no contraindication. For most patients this entailed underuse of one drug, but 17 (6%) of patients received no treatment. beta Blockers were 2.5 times less likely to be used than aspirin. Treatment was not associated with the age or sex of the patient, risk of further infarction, or hospital of discharge. Secondary prophylaxis after myocardial infarction is practised haphazardly. It should be offered to all patients who can tolerate it, after a trial period to assess any side effects of the drugs if necessary.


Complete nucleotide sequence of a cloned chicken alpha-globin cDNA.
Chicken globin double-stranded cDNA was synthesised from anaemic adult reticulocyte alpha- and beta-globin mRNA and ligated into the Hind III site of pBR322 using synthetic Hind III decamers. Transformation of E. coli x1776 resulted in the production of a number of alpha- and beta-cDNA clones. One of the alpha-type clones (pCG alpha-8) was fully sequenced and found to code for neither alpha A- nor alpha D-globin. Partial sequencing of the other alpha-cDNA clones indicates that they are all of the same type.


Say NO to ROS: Their Roles in Embryonic Heart Development and Pathogenesis of Congenital Heart Defects in Maternal Diabetes.
Congenital heart defects (CHDs) are the most prevalent and serious birth defect, occurring in 1% of all live births. Pregestational maternal diabetes is a known risk factor for the development of CHDs, elevating the risk in the child by more than four-fold. As the prevalence of diabetes rapidly rises among women of childbearing age, there is a need to investigate the mechanisms and potential preventative strategies for these defects. In experimental animal models of pregestational diabetes induced-CHDs, upwards of 50% of offspring display congenital malformations of the heart, including septal, valvular, and outflow tract defects. Specifically, the imbalance of nitric oxide (NO) and reactive oxygen species (ROS) signaling is a major driver of the development of CHDs in offspring of mice with pregestational diabetes. NO from endothelial nitric oxide synthase (eNOS) is crucial to cardiogenesis, regulating various cellular and molecular processes. In fact, deficiency in eNOS results in CHDs and coronary artery malformation. Embryonic hearts from diabetic dams exhibit eNOS uncoupling and oxidative stress. Maternal treatment with sapropterin, a cofactor of eNOS, and antioxidants such as N-acetylcysteine, vitamin E, and glutathione as well as maternal exercise have been shown to improve eNOS function, reduce oxidative stress, and lower the incidence CHDs in the offspring of mice with pregestational diabetes. This review summarizes recent data on pregestational diabetes-induced CHDs, and offers insights into the important roles of NO and ROS in embryonic heart development and pathogenesis of CHDs in maternal diabetes.


Timed motor tests can detect subtle motor dysfunction in early Parkinson's disease.
Early diagnosis of Parkinson's disease (PD) is important for putative neuroprotective therapies to be initiated in the earliest stage of the disease. We investigated whether a previously validated timed motor test (TMT) battery could detect subtle motor dysfunction in early PD patients and even in clinically unaffected limbs of strictly hemiparkinsonian patients. We assessed 107 PD patients (symptom duration <or=2 years; dopa-naive) and 100 healthy, age-matched controls with eight simple TMTs based on aspects of (a) walking, (b) writing, (c) single and double-handed pegboard performance, (d) finger tapping, and (e) diadochokinesis. We evaluated the ability of individual and combined TMTs to discriminate patients from controls using ROC curves. Second, we investigated whether these TMTs could identify motor dysfunction of the clinically unaffected limb in 42 strictly hemiparkinsonian patients. The pegboard dexterity test had the best ROC curve (AUC 0.97; 95% sensitivity, 89% specificity) for patients versus controls. It retained reasonable accuracy when testing the clinically unaffected limb of hemiparkinsonian patients versus the mean of right and left-hand scores in controls (AUC 0.73). The pegboard dexterity test is a sensitive and inexpensive instrument to detect motor dysfunction in early PD. Therefore, it may be worth evaluating as a diagnostic tool in everyday clinical practice to assess patients with early symptomatic PD, or as part of a more elaborate screening battery in a defined population at risk.


Primary Clear Cell Chondrosarcoma of Thoracic Spine.
Clear cell chondrosarcoma is a rare cartilaginous tumor that arises commonly in the epiphyses of the proximal femur or humerus. Spinal involvement is extremely rare, but when present, it most frequently involves the thoracic spine. Clear cell chondrosarcoma is rarely reported in thoracic spine. We report a case of a 70-year-old man with clear cell chondrosarcoma of the T7-8 thoracic spine. Gross en bloc resection of T6-8 vertebral bodies with reconstruction and fusion followed by radiotherapy were performed.


Detailed analysis of the oligodendrocyte myelin glycoprotein gene in four patients with neurofibromatosis 1 and primary progressive multiple sclerosis.
Neurofibromatosis 1 (NF1) is a common autosomal disorder with a wide range of neurological manifestations. The case histories of five patients, including two siblings, are reported who have both neurofibromatosis 1 and primary progressive multiple sclerosis (PPMS). A further patient with both NF1 and PPMS has since been identified. More recently, a systematic clinical review of 138 unselected adult patients with NF1 identified one patient with a slowly progressive spastic paraparesis and multiple high signal hyperintensities on T2 weighted MRI. Molecular genetic studies suggest a mechanism by which the clinical association of progressive white matter disease and NF1 might arise. The gene for NF1 is located on chromosome 17q, spans 350 kb of genomic DNA, and contains 60 exons. The gene for oligodendrocyte myelin glycoprotein (OMgp) is embedded within intron 27b of the NF1 gene. OMgp is a membrane glycoprotein that appears in the human CNS at the time of myelination. It can be detected immunohistochemically on CNS myelin and on the surface of cultured oligodendrocytes. Structurally, OMgp has the potential to function as an adhesion molecule and could contribute to the interactions between the plasma membranes of oligodendrocytes and axons required for myelination and/or axon survival. This study considers the specific hypothesis that PPMS in patients with NF1 results from concurrent mutation of the OMgp gene. The OMgp genes of four unrelated patients with NF1 and PPMS were examined using a combination of Southern blot, dosage polymerase chain reaction, and chemical cleavage of mismatch. The entire OMgp coding sequence, all intronic sequence, the intron-exon boundaries, and 1 kb of flanking sequence were screened. The DNA from two patients was found to contain an alteration in the OMgp gene resulting in an amino acid change of glycine to aspartic acid at codon 21. It is concluded that PPMS in patients with NF1 can occur without concurrent mutation of the OMgp gene. The glycine to aspartic acid polymorphic alteration at codon 21 is neither sufficient nor necessary for the development of PPMS.


Comparison of injectate spread and nerve involvement between retrolaminar and erector spinae plane blocks in the thoracic region: a cadaveric study.
Although different injection locations for retrolaminar and erector spinae plane blocks have been described, the two procedures have a similar anatomical basis. In this cadaveric study we compared anatomical spread of dye in the thoracic region following these two procedures. Following randomisation, 10 retrolaminar blocks and 10 erector spinae plane blocks were performed on the left or right sides of 10 unembalmed cadavers. For each block, 20 ml of dye solution was injected at the T5 level. The back regions were dissected and the involvement of the thoracic spinal nerve was also investigated. Twenty blocks were successfully completed. A consistent vertical spread, with deep staining between the posterior surface of the vertebral laminae and the overlaying transversospinalis muscle was observed in all retrolaminar blocks. Moreover, most retrolaminar blocks were predominantly associated with fascial spreading in the intrinsic back muscles. With an erector spinae plane block, dye spread in a more lateral pattern than with retrolaminar block, and fascial spreading in the back muscles was also observed. The number of stained thoracic spinal nerves was greater with erector spinae plane blocks than with retrolaminar blocks; median 2.0 and 3.5, respectively. Regardless of technique, the main route of dye spread was through the superior costotransverse ligament to the ipsilateral paravertebral space. Although erector spinae plane blocks were associated with a slightly larger number of stained thoracic spinal nerves than retrolaminar blocks, both techniques were consistently associated with posterior spread of dye and with limited spread to the paravertebral space.


Induced pluripotent stem cells as a tool for comparative physiology: lessons from the thirteen-lined ground squirrel.
Comparative physiologists are often interested in adaptive physiological phenomena found in unconventional model organisms; however, research on these species is frequently constrained by the limited availability of investigative tools. Here, we propose that induced pluripotent stem cells (iPSCs) from unconventional model organisms may retain certain species-specific features that can consequently be investigated in depth in vitro; we use hibernating mammals as an example. Many species (including ground squirrels, bats and bears) can enter a prolonged state of physiological dormancy known as hibernation to survive unfavorable seasonal conditions. Our understanding of the mechanisms underpinning the rapid transition and adaptation to a hypothermic, metabolically suppressed winter torpor state remains limited partially because of the lack of an easily accessible model. To address the fascinating unanswered questions underlying hibernation biology, we have developed a powerful model system: iPSCs from a hibernating species, the thirteen-lined ground squirrel (Ictidomys tridecemlineatus). These stem cells can potentially be differentiated into any cell type, and can be used for the analysis of cell-autonomous mechanisms that facilitate adaptation to hibernation and for comparisons with non-hibernators. Furthermore, we can manipulate candidate molecular and cellular pathways underlying relevant physiological phenomena by pharmacological or RNAi-based methods, and CRISPR/Cas9 gene editing. Moreover, iPSC strategies can be applied to other species (e.g. seals, naked mole rats, humming birds) for in vitro studies on adaptation to extreme physiological conditions. In this Commentary, we discuss factors to consider when attempting to generate iPSCs from unconventional model organisms, based on our experience with the thirteen-lined ground squirrel.


Pressure effects on the abiotic polymerization of glycine.
Polymerization experiments were performed using dry glycine under various pressures of 5-100 MPa at 150 degrees C for 1-32 days. The series of experiments was carried out under the assumption that the pore space of deep sediments was adequate for dehydration polymerization of pre-biotic molecules. The products show various colors ranging from dark brown to light yellow, depending on the pressure. Visible and infrared spectroscopy reveal that the coloring is the result of formation of melanoidins at lower pressures. High-performance liquid chromatography and mass spectrometry analyses of the products show that: (1) glycine in all the experimental runs oligomerizes from 2-mer to 10-mer; (2) the yields are dependent on pressure up to 25 MPa and decrease slightly thereafter; and (3) polymerization progressed for the first 8 days, while the amounts of oligomers remained constant for longer-duration runs of up to 32 days. These results suggest that pressure inhibits the decomposition of amino acids and encourages polymerization in the absence of a catalyst. Our results further imply that abiotic polymerization could have occurred during diagenesis in deep sediments rather than in oceans.


Definition and validation of a system for classifying the undersized Corail femoral stem in total hip arthroplasty.
The uncemented total hip arthroplasty relies on a secure initial fixation of the femoral stem to achieve osseointegration. Undersizing of the femoral implant compromises this. Surgeons routinely review postoperative radiographs to assess appropriate sizing, but existing methods of assessment lack standardisation. We present a system of accurately and reliably classifying radiological undersizing, which will help us better understand the factors that might have led to undersizing. To describe and evaluate a classification system for assessing radiological undersizing of the uncemented stem in hip arthroplasty. We conducted a retrospective review of 1,337 consecutive hip arthroplasties using the Corail stem. Two independent investigators reviewed post-operative radiographs and classified them as either appropriately sized or undersized. Undersized stems were sub-categorised into four subtypes: uniformly undersized, varus undersized, valgus undersized or 'cocktail-glass' undersized. Inter- and intra-observer agreement was determined. The accuracy of our classification system was validated by comparison with digital re-templating. We further assessed patient demographics and stem size in relation to sizing. 1 in 5 cases (19.75%) were deemed radiologically undersized. The commonest subtypes of undersizing were uniformly (47%) and varus (39%) undersized. When assessing sizing and subtype categorisation, inter-observer agreement was 89-92% and intra-observer agreement 86%. Classification decisions showed 92% and 97% accuracy for uniformly undersizing and varus undersizing respectively when validated against digital re-templating. Age, gender and smaller stem size were significantly associated with radiological undersizing. The Corail KLA model (125° neck) was found to have a higher incidence of stems undersized in varus. This study describes and validates a classification system for the analysis of radiological undersizing.


Physical activity and exercise training: a relevant aspect of the dialysis patient's care.
Sedentary lifestyle is frequent in hemodialysis patients whose physical capabilities are largely reduced when compared with healthy subjects, and evidence exists that sedentary dialysis patients are at higher risk of death as compared to non-sedentary ones. Dialysis patients may suffer from cardiovascular disease, diabetes, malnutrition, depression, which limits their exercise capacity; conversely, regular physical exercise may favor rehabilitation and correction of several cardiovascular, metabolic and nutritional abnormalities. Many observational, population-based studies show that the level of physical activity is related to quality of life and nutritional status, as well as to the survival probability. Intervention studies are instead lacking; a randomized controlled multicenter trial is in progress in Italy to assess the effect of home-based exercise programs on survival and hospitalization rate in stable dialysis patients. Implementation of physical activity should be one of the goals of dialysis care management, but several barriers prevent a widespread implementation of physical exercise programs in the dialysis units. A lack of patients' or care-givers' motivation or willingness, and structural or functional resources are the most frequent obstacles to exercise implementation. Since the hemodialysis population is quite heterogeneous for physical abilities and comorbidities, exercise in not for everyone and individual prescription is required for a correct and safe implementation of physical activity.


[Brazilian scientific production on the Family Health Strategy and the change in the model of care].
The variety of existing studies addressing the Family Health Strategy (ESF) and its role in the reorientation of the model of care in the country has motivated the systematization of the advances and limitations described in these studies. Thus, this study, from a review of the scientific production on this theme, analyzed if the ESF has been able to modify the model of care. Forty-one articles from the Scielo database published between 2002 and 2010 that fulfilled the inclusion criteria were analyzed. They were fully analyzed in terms of political-institutional, organizational or technical-care dimensions. The results show that despite the improvement in the work process in primary care, its replacement aspect was not seen in the majority of the studies. Universal expansion of access to the health services, extension of coverage and focus were predominant. The changes are observed when analyzed in light of the demand, with better attendance and connectivity. The most evident limits are in the lack of focus on health needs, as in the territorial issue, community participation and the social determinants addressed in an intersectoral way. Different degrees of the implementation of strategy were identified, though they have not yet resulted in system reorganization at local level.


CAKbeta/Pyk2 kinase is a signaling link for induction of long-term potentiation in CA1 hippocampus.
Long-term potentiation (LTP) is an activity-dependent enhancement of synaptic efficacy, considered a model of learning and memory. The biochemical cascade producing LTP requires activation of Src, which upregulates the function of NMDA receptors (NMDARs), but how Src becomes activated is unknown. Here, we show that the focal adhesion kinase CAKbeta/Pyk2 upregulated NMDAR function by activating Src in CA1 hippocampal neurons. Induction of LTP was prevented by blocking CAKbeta/Pyk2, and administering CAKbeta/Pyk2 intracellularly mimicked and occluded LTP. Tyrosine phosphorylation of CAKbeta/Pyk2 and its association with Src was increased by stimulation that produced LTP. Finally, CAKbeta/Pyk2-stimulated enhancement of synaptic AMPA responses was prevented by blocking NMDARS, chelating intracellular Ca(2+), or blocking Src. Thus, activating CAKbeta/Pyk2 is required for inducing LTP and may depend upon downstream activation of Src to upregulate NMDA receptors.


[1910-1911, a crucial biennium in the history of the Asociación Española de Urología (I). How our association was born].
Although the background and major details concerning the events that in 1911 culminated with the creation of the Spanish Association of Urology are well known as they have been published earlier in several papers, until now and as far as we know, no paper had presented the dates and particulars of the preparatory and constituent meetings of the Society, the first Regulations, and the semblance and biographies of the project's main inspirators and initiators. This article, prepared with abundant material from newspapers and literature of the period, extricated from the resources of the National Library and the archives of the Royal Academy of Medicine in Madrid, uncovers some unpublished data on the foundation and its advocates, and rediscovers other that although published in journals at the beginning of the century, remained forgotten or were unknown for most urologists. In this way, we complete the history of a part of our past, perhaps the most interesting one, and that of its main players.